The mechanisms by which phagocytic cells (including granulocytes, monocytes, and macrophages) function in protecting the human host from bacterial and fungal infection and their alteration in various pathologic states is the concern of the proposed investigations. Information will be gathered by several approaches including: 1) screening individuals with a history of repeated pyogenic infections for leukocyte functional defects and further characterizing these as indicated; 2) examining the mechanisms involved in the production and utilization of the microbicidal substance H2O2 by those cells. Particular attention will be paid to the distinct possibility that receptors on the phagocytic cell membrane which participate in particle ingestion also serve to trigger H2O2 formation. Studies on normal cells will be extended to patients with impaired synthesis of H2O2, chronic granulomatous disease of childhood, to discover and perhaps correct their defects; 3) investigation of the metabolic and lysosomal mechanisms involved in the bactericidal activity of macrophages derived from human blood monocytes and other sources, and study of how these mechanisms are affected in various immune states. The purpose of these investigation is to provide a better understanding of the normal antibacterial mechanisms in granulocytes and macrophages, and how they might be altered in various pathologic states characterized by recurrent infection. Such knowledge could lead to the development of means to augment these mechanisms and to correct abnormalities in specific disease states.